The purpose of the proposed research is to investigate the actions of the neurotoxin, quinolinic acid, on the GABAergic system. Quinolinic acid has been demonstrated to induce lesions in rodent brain that resemble the neurodegeneration observed in brains of patients with Huntington's Disease. Huntington's Disease is characterized by severe dementia and motor disturbances. The primary genetic defect underlying these symptoms is poorly understood. I propose to investigate possible interactions of quinolinic acid with the GABAbenzodiazepine-barbiturate complex. This will be accomplished by examining the effects of quinolinic acid on receptor binding in membranes prepared from mouse brain. Preliminary studies indicate that quinolinic acid enhances benzodiazepine binding in such membrane preparations. Additionally, the effects of chronic quinolinic acid treatment on fetal mouse brain reaggregate cultures will be examined. These cultures may provide a good model system in which to study molecular mechanisms responsible for deficits in human genetic diseases and in which human serum, CSF, or brain extract samples could be screened for neurotoxic agents.